New Analysis Strengthens Cardiovascular Safety Profile of Abaloparatide

July 14, 2020

A new analysis is strengthening the safety profile of abaloparatide (Tymlos) in postmenopausal women to prevent risk of fracture.

A recent study analyzing data from a pair of phase 3 studies and healthy controls is shedding additional light on the safety of an osteoporosis drug used in postmenopausal women.

Results of the study, which examined data from the ACTIVE and ACTIVExtend trials, supports the use of abaloparatide (Tymlos) in postmenopausal women at high risk of fracture without these patients incurring additional cardiovascular risk.

“Treatment with abaloparatide and teriparatide resulted in a transient increase in HR and a small decrease in 1 hour post-dose BP. These changes were not associated with an increase in serious cardiac AEs evaluated in ACTIVE, MACE, or heart failure in postmenopausal women with osteoporosis,” wrote study investigators.

Having received approval for the treatment of postmenopausal osteoporosis from the US Food and Drug Administration back in 2017, some clinicians still had questions in regard to the cardiovascular safety profile of the parathyroid hormone analog. With this in mind, investigators designed an analysis to assess the cardiovascular safety profile by evaluating heart rate, blood pressure, and cardiovascular-related adverse events from participants in the ACTIVE AND ACTIVExtend trials.

ACTIVE was designed as a randomized, double-blind, placebo- and active-controlled, multicenter phase 3 trial. Participants in the trial were postmenopausal women between the ages of 49-86 years old. In total, 2460 participants were included in the trial. Women included in this 18-month trial were randomized to daily subcutaneous abaloparatide 80 µg, matching placebo, or open-label daily subcutaneous teriparatide 20 µg.

ACTIVExtend was designed as an open-label extension of the original ACTIVE trial. Participants were enrolled after a 1-month treatment-free period and were transitioned to open-label alendronate in a 70 mg dose once-weekly for 24 months. Additionally, 55 healthy adults were included in a pharmacology study.

Of note, patients included in these trials were required to have a sitting systolic blood pressure between 100-155 mmHg, diastolic blood pressure between 40-95 mmHg, and a heart rate between 45-100 beats per minute. These measurements were conducted at visit 1 of the original ACTIVE trial.

Following first dosing, mean heart rate change from pre-treatment to 1-hour post-treatment was 7.9 (8.5) bears per minute for abaloparatide, 5.3 (7.5) for teriparatide, and 1.2 (7.1) for placebo. Investigators pointed out a similar pattern was observed when examining heart rate in subsequent visits. Among those included in the healthy volunteers group, the observed increase in heart rate resolved within 4 hours.

When examining effects on sitting systolic and diastolic blood pressure, investigators observed a mean change of -2.7 mmHg and -3.6 mmHg, respectively among those receiving abaloparatide. Change among those receiving teriparatide experienced mean reductions of -2.0 and -3.6 mmHg, respectively, and those in the placebo group experienced mean reductions of -1.5 and -2.3 mmHg.

When assessing the prevalence of serious cardiovascular adverse events, rate of participants experiencing such an event was similar across all groups and ranged from 0.9%-1.0%. Results of the posthoc analysis indicated time-to-first incidence of major adverse cardiovascular events and heart failure was greater with abaloparatide (P=.02) and teriparatide (P=.004) than placebo.

This study, “Cardiovascular Safety of Abaloparatide in Postmenopausal Women with Osteoporosis: Analysis from the ACTIVE Phase 3 Trial,” was published in The Journal of Clinical Endocrinology and Metabolism.